This invention relates to improved water-soluble hydrogels which are in the form of macromer-crosslinked polymers of one or more water-soluble monoolefinic monomers, optionally containing a minor amount of one or more water-insoluble monoolefinic monomers having superior active agent loading capacity. The macromer component is a terminally diolefinic hydrophobic macromer containing a polypropylene oxide or polytetramethylene oxide diradical in the macromer chain. These hydrogels can be loaded with active agents, especially biologically active agents, including pharmaceuticals, insecticides, herbicides, and the like, for the controlled, sustained release thereof by diffusion upon contact with an aqueous environment.
Hydrophilic hydrogels in the form of macromer-crosslinked polymers containing monomer and macromer components are known, for example, in U.S. Pat. No. 4,177,056, the disclosure of which is incorporated herein by reference in toto in regard to eligible components, including active agents, monomers and macromers; polymer preparation, including process parameters and modes of preparation; active agent loading techniques, and the use thereof; and preferred embodiments in respect to such components, preparation, loading techniques, and use.
It has been surprisingly and unexpectedly discovered, in accordance with the instant invention, that the nature of the macromer-crosslinked polymers can be substantially and irrevocably modified so as to increase the organic solvent swelling characteristics of the polymers. As a result, the amount of organic solvent soluble active agent capable of being loaded into such polymers can be greatly increased.
This modification of the macromer-crosslinked polymers is obtained by conducting the polymerization in the presence of certain macromer compatible compounds. Such compounds act as macromer expanders by increasing the organic solvent soluble active agent loadability. But, by virtue of their solubility in the macromer component, both prior to and during polymerization, the macromer expanding compounds do not occasion the formation of copolymers having a macroporous structure. Macroporous copolymers are generally characterized in having pores ranging from about 100-5000 Angstroms. Various cross-linked macroporous polymers are disclosed, for example, in U.S. Pat. No. 3,509,078. In contrast to macroporous copolymers, the instant macromer expanded copolymers are substantially free from macroporosity. As a result, the instant glossy, i.e., optically clear to hazy, copolymers release the active agent by controlled diffusion upon contact with an aqueous environment, in contrast to convectional paths and the like, occasioned by macroporous networks.
It is an object of the present invention to provide novel macromer expanded hydrogel polymers having substantially increased organic solvent soluble active agent loadability and their preparation and use.
It is a further object of the present invention to provide active agent loaded controlled, sustained release compositions of such polymers and their preparation and use.
These and other objects of the present invention are apparent from the following description.